Are febrile seizures an indication for intermittent benzodiazepine treatment, and if so, in which cases?
Febrile seizures occur in ∼4% of children. After a first febrile seizure, the risk of recurrence is ∼40%, but excellent studies document that febrile seizures do not cause brain damage or deficits in cognition or behaviour. The risk of subsequent epilepsy is 2-4%. Prolonged febrile seizures are of concern because a child may later develop mesial temporal sclerosis and intractable epilepsy in rare cases. Most prolonged febrile seizures represent the first febrile seizure and cannot be anticipated. A first prolonged febrile seizure does not increase the risk of recurrence, but if there is a recurrence, it is more likely to be prolonged. Prevention of recurrent febrile seizures is difficult. Antipyretics are ineffective. Daily AED treatment is not often justified. Intermittent oral diazepam at the time of illness is not very successful and has significant side effects. The most optimistic study found that the number of subjects required to treat in order to prevent one recurrence was 14. Intermittent clobazam has fewer side effects than diazepam and may be somewhat effective. Rescue benzodiazepines given outside health care facilities may be effective in selected patients to prevent prolonged recurrences, although this has not been proven with rectal diazepam which has been more extensively studied than buccal or nasal midazolam. Currently, we suggest that, for children with febrile seizures, candidates for consideration for rescue benzodiazepines are those with a prolonged febrile seizure or poor access to medical care. It is possible that the use of a rescue benzodiazepine may alleviate severe parental anxiety, but this remains to be established.


DNA damage and S phase-dependent E2F1 stabilization requires the cIAP1 E3-ubiquitin ligase and is associated with K63-poly-ubiquitination on lysine 161/164 residues.
The E2F transcription factor 1 is subtly regulated along the cell cycle progression and in response to DNA damage by post-translational modifications. Here, we demonstrated that the E3-ubiquitin ligase cellular inhibitor of apoptosis 1 (cIAP1) increases E2F1 K63-poly-ubiquitination on the lysine residue 161/164 cluster, which is associated with the transcriptional factor stability and activity. Mutation of these lysine residues completely abrogates the binding of E2F1 to CCNE, TP73 and APAF1 promoters, thus inhibiting transcriptional activation of these genes and E2F1-mediated cell proliferation control. Importantly, E2F1 stabilization in response to etoposide-induced DNA damage or during the S phase of cell cycle, as revealed by cyclin A silencing, is associated with K63-poly-ubiquitinylation of E2F1 on lysine 161/164 residues and involves cIAP1. Our results reveal an additional level of regulation of the stability and the activity of E2F1 by a non-degradative K63-poly-ubiquitination and uncover a novel function for the E3-ubiquitin ligase cIAP1.


Project LIFE--Learning to Improve Fitness and Function in Elders: methods, design, and baseline characteristics of randomized trial.
Insufficient levels of physical activity have significant clinical consequences. Primary care settings typically do not emphasize physical activity counseling. We describe the design, methods, and baseline characteristics of "Learning to Improve Fitness and Function in Elders," a two-armed randomized controlled trial that assesses whether physical activity counseling improves the physical function of older veterans. A physical activity counseling program, partially administered by primary care providers, advocating 30 min of walking 5 days a week and 15 min of lower-limb strength training 3 days a week will be compared with usual care. The multicomponent counseling program consists of yearlong (1) telephone counseling, (2) automated and in-person provider counseling, and (3) tailored mailed materials. Physical activity will be assessed with the Community Healthy Activities Model Program for Seniors. Physical function will be assessed by gait speed (primary end point), 400 m walk time, chair stands, balance tests, and self-reported physical function and disability. Self-reports of chronic illness, symptoms, pain, health-related quality of life, self-efficacy, and motivation will also be assessed. A total of 400 veterans, aged 70 to 92, have enrolled and are currently receiving multicomponent physical activity counseling or usual care.


Phosphatidylinositol 4,5-bisphosphate hydrolysis mediates histamine-induced KCNQ/M current inhibition.
The M-type potassium channel, of which its molecular basis is constituted by KCNQ2-5 homo- or heteromultimers, plays a key role in regulating neuronal excitability and is modulated by many G protein-coupled receptors. In this study, we demonstrate that histamine inhibits KCNQ2/Q3 currents in human embryonic kidney (HEK)293 cells via phosphatidylinositol 4,5-bisphosphate (PIP(2)) hydrolysis mediated by stimulation of H(1) receptor and phospholipase C (PLC). Histamine inhibited KCNQ2/Q3 currents in HEK293 cells coexpressing H(1) receptor, and this effect was totally abolished by H(1) receptor antagonist mepyramine but not altered by H(2) receptor antagonist cimetidine. The inhibition of KCNQ currents was significantly attenuated by a PLC inhibitor U-73122 but not affected by depletion of internal Ca(2+) stores or intracellular Ca(2+) concentration ([Ca(2+)](i)) buffering via pipette dialyzing BAPTA. Moreover, histamine also concentration dependently inhibited M current in rat superior cervical ganglion (SCG) neurons by a similar mechanism. The inhibitory effect of histamine on KCNQ2/Q3 currents was entirely reversible but became irreversible when the resynthesis of PIP(2) was impaired with phosphatidylinsitol-4-kinase inhibitors. Histamine was capable of producing a reversible translocation of the PIP(2) fluorescence probe PLC(delta1)-PH-GFP from membrane to cytosol in HEK293 cells by activation of H(1) receptor and PLC. We concluded that the inhibition of KCNQ/M currents by histamine in HEK293 cells and SCG neurons is due to the consumption of membrane PIP(2) by PLC.


A bilobal model of Ca2+-dependent inactivation to probe the physiology of L-type Ca2+ channels.
L-type calcium channels (LTCCs) are critical elements of normal cardiac function, playing a major role in orchestrating cardiac electrical activity and initiating downstream signaling processes. LTCCs thus use feedback mechanisms to precisely control calcium (Ca2+) entry into cells. Of these, Ca2+-dependent inactivation (CDI) is significant because it shapes cardiac action potential duration and is essential for normal cardiac rhythm. This important form of regulation is mediated by a resident Ca2+ sensor, calmodulin (CaM), which is comprised of two lobes that are each capable of responding to spatially distinct Ca2+ sources. Disruption of CaM-mediated CDI leads to severe forms of long-QT syndrome (LQTS) and life-threatening arrhythmias. Thus, a model capable of capturing the nuances of CaM-mediated CDI would facilitate increased understanding of cardiac (patho)physiology. However, one critical barrier to achieving a detailed kinetic model of CDI has been the lack of quantitative data characterizing CDI as a function of Ca2+ This data deficit stems from the experimental challenge of uncoupling the effect of channel gating on Ca2+ entry. To overcome this obstacle, we use photo-uncaging of Ca2+ to deliver a measurable Ca2+ input to CaM/LTCCs, while simultaneously recording CDI. Moreover, we use engineered CaMs with Ca2+ binding restricted to a single lobe, to isolate the kinetic response of each lobe. These high-resolution measurements enable us to build mathematical models for each lobe of CaM, which we use as building blocks for a full-scale bilobal model of CDI. Finally, we use this model to probe the pathogenesis of LQTS associated with mutations in CaM (calmodulinopathies). Each of these models accurately recapitulates the kinetics and steady-state properties of CDI in both physiological and pathological states, thus offering powerful new insights into the mechanistic alterations underlying cardiac arrhythmias.


Antitumor Activities of Rauwolfia vomitoria Extract and Potentiation of Gemcitabine Effects Against Pancreatic Cancer.
Pancreatic cancer is one of the most lethal malignancies with very limited treatment option. In the effort of enhancing the effect of the conventional chemotherapeutic drug gemcitabine against pancreatic cancer, we investigatedin vitroandin vivothe anticancer effect of a β-carboline-enriched extract from the plantRauwolfia vomitoria(Rau), either alone or in combination with gemcitabine, in preclinical pancreatic cancer models. Rau induced apoptosis in pancreatic cancer cells in a concentration-dependent manner, and completely inhibited colony formation of PANC-1 cells in soft agar. The combination of Rau and gemcitabine had synergistic effect in inhibiting cell growth with dose reduction effect for gemcitabine. In an orthotopic pancreatic cancer mouse model, PANC-1 tumor growth was significantly suppressed by Rau treatment. Metastasis was inhibited by Rau. Adding Rau to gemcitabine treatment reduced tumor burden and metastatic potential in the gemcitabine non-responsive tumor. These data suggest that Rau possesses anti-pancreatic cancer activity and could improve effect of gemcitabine.


Effectively training the hospice and palliative medicine physician workforce for improved end-of-life health care in the United States.
The widening gap between the demand for palliative care services and the supply of trained palliative care professionals has resulted in considerable end-of-life distress for patients. Without formal training in palliative medicine and end-of-life symptom management, physicians in the United States are less equipped to competently address seriously ill and dying patients' medical, emotional, and spiritual needs. Recent attempts within graduate medical education training deliberately seek to prepare a critical mass of physicians as the new hospice and palliative medicine workforce in the United States. In addition, healthcare reform proposals may re-define the National Health Service Corps (NHSC) post-graduate training over the next five years and the Hospice Medicare Benefit altogether. Healthcare policy options include steady changes at multiple levels of medical training -namely, medical school curriculum mandates, requiring all graduate physician residency training to foster patient-centered communication skills and discussions about advanced directives, and instituting palliative medicine proficiency Continuing Medical Education (CME) requirements for all states' medical licensing boards. Attracting qualified physicians to serve patients at the end of life, innovative medical school loan repayment programs and scholarships will also foster excellence in the field of hospice and palliative medicine. Correcting our current paucity of formal training in palliative medicine better utilizes hospice and restores patients' dignity at the end of life.


Glioblastoma cytotoxicity conferred through dual disruption of endolysosomal homeostasis by Vacquinol-1.
Increased membrane trafficking is observed in numerous cancer types, including glioblastoma. Targeting the oncogenic driven acquired alterations in membrane trafficking by synthetic cationic amphiphilic small molecules has recently been shown to induce death of glioblastoma cells, although the molecular targets are unknown. The mechanism of action of the cationic amphiphilic drug Vacquinol-1 (Vacq1)-induced cytotoxicity was investigated using cell biology, biochemistry, functional experiments, chemical biology, unbiased antibody-based post-translation modification profiling, and mass spectrometry-based chemical proteomic analysis on patient-derived glioblastoma cells. Vacq1 induced two types of abnormal endolysosomal vesicles, enlarged vacuoles and acidic vesicle organelles (AVOs). Mechanistically, enlarged vacuoles were formed by the impairment of lysosome reformation through the direct interaction and inhibition of calmodulin (CaM) by Vacq1, while AVO formation was induced by Vacq1 accumulation and acidification in the endosomal compartments through its activation of the v-ATPase. As a consequence of v-ATPase activation, cellular ATP consumption markedly increased, causing cellular energy shortage and cytotoxicity. This effect of Vacq1 was exacerbated by its inhibitory effects on calmodulin, causing lysosomal depletion and a failure of acidic vesicle organelle clearance. Our study identifies the targets of Vacq1 and the mechanisms underlying its selective cytotoxicity in glioblastoma cells. The dual function of Vacq1 sets in motion a glioblastoma-specific vicious cycle of ATP consumption resulting in cellular energy crisis and cell death.


Expression of kisspeptins and kisspeptin receptor in the kidney of chronic renal failure rats.
Kisspeptins are biologically active cleavage peptides of the KiSS-1 gene products with important roles in the suppression of tumor metastasis and in the reproduction. The aim of the present study is to clarify changes of the expression of kisspeptins and kisspeptin receptor in the kidney with and without chronic renal impairment. 5/6 nephrectomized rats were used as the rat model of chronic renal failure. Competitive quantitative RT-PCR showed that kisspeptin mRNA levels were decreased in the kidney of 5/6 nephrectomized rats at 56 days compared with sham-operated rats. In contrast, immunoreactive kisspeptin concentrations were increased in the kidney of 5/6 nephrectomized rats at 56 days. On the other hand, kisspeptin receptor mRNA levels were increased in the kidney of 5/6 nephrectomized rats at 14 and 56 days compared with sham-operated rats. Immunocytochemistry showed that kisspeptins and kisspeptin receptor were expressed in renal tubular cells, collecting duct cells, vascular smooth muscle cells in both rats. The intensity of kisspeptin receptor immunostaining was lower in 5/6 nephrectomized rats than in sham-operated rats. Western blot analysis confirmed that kisspeptin receptor protein levels were significantly decreased in the remnant kidney of 5/6 nephrectomized rats (about 23% of sham-operated rats), which is a good contrast to the kisspeptin receptor mRNA expression. The present study has shown that expression of kisspeptins and kisspeptin receptor are altered in the kidney tissues of chronic renal impairment, raising the possibility of their pathophysiological roles in chronic renal failure.


Transcriptome profiling of the response of Mycosphaerella graminicola isolates to an azole fungicide using cDNA microarrays.
SUMMARY Resistance to azole antifungals is a major problem in the control of diseases caused by fungal pathogens of both humans and plants. Potential for the development of azole resistance in the wheat leaf blotch pathogen Mycosphaerella graminicola, the causal agent of the most economically significant foliar disease of wheat in north-western Europe, is now of particular concern after the recent emergence of widespread resistance to quinone outside inhibitor fungicides. Using a cDNA microarray representing around 25% of the genome, we have profiled the transcriptional response of M. graminicola to epoxiconazole, currently the most widely used azole fungicide on cereal crops. By comparing the transcription profiles of two M. graminicola isolates with contrasting sensitivities to epoxiconazole we show qualitative and quantitative differences in differentially expressed genes, including those involved in ergosterol biosynthesis, mitochondrial respiration and transport mechanisms. This represents the first study investigating the response of a plant pathogenic fungus to a fungicide using cDNA microarray technology.


Lifting the lid on GPCRs: the role of extracellular loops.
GPCRs exhibit a common architecture of seven transmembrane helices (TMs) linked by intracellular loops and extracellular loops (ECLs). Given their peripheral location to the site of G-protein interaction, it might be assumed that ECL segments merely link the important TMs within the helical bundle of the receptor. However, compelling evidence has emerged in recent years revealing a critical role for ECLs in many fundamental aspects of GPCR function, which supported by recent GPCR crystal structures has provided mechanistic insights. This review will present current understanding of the key roles of ECLs in ligand binding, activation and regulation of both family A and family B GPCRs.


[The effect of triamcinolone acetonide on the liver mitochondria in endotoxemia].
Endotoxin Salmonella typhimurium (LD50) was administered intraperitoneally to mice. It was shown that triamcinolone acetonide in a dose of 1 mg/kg living weight administered to mice 1 hour before endotoxin administration completely prevents the death of the animals and decreases the level of changes in the activities of enzymes of glutamate dehydrogenase, succinate dehydrogenase, monoaminoxidase, cytochrome oxidase in the liver mitochondria in endotoxemia. The level of lipid peroxidation in mitochondria during endotoxemia against the background of triamcinolone acetonide action is close to control. The use of triamcinolone acetonide in the absence of the effect of endotoxin results in an insignificant damage of mitochondrial membranes.


Ascertaining Design and Implementation Requirements for a Perioperative Neurocognitive Training Intervention for the Prevention of Persistent Pain After Surgery.
Persistent postsurgical pain (PPSP) is a common complication that impacts quality of life, often necessitating long-term opioid treatment. Certain neurocognitive factors, including reduced performance on cognitive flexibility tasks, are associated with increased risk of PPSP. We examine the perceptions of surgical patients and clinicians with regard to perioperative pain management activities and needs; patient acceptance and use of a perioperative neurocognitive training intervention; and implementation feasibility. We conducted both individual and focus group interviews with patients undergoing thoracic surgery and clinicians in an academic medical center. The Consolidated Framework for Intervention Research guided the development of interview questions related to the adoption and implementation of a neurocognitive intervention to mitigate PPSP. A thematic analysis was used to analyze the responses. Forty patients and 15 clinicians participated. Interviews revealed that there is minimal discussion between clinicians and patients about PPSP. Most participants were receptive to a neurocognitive intervention to prevent PPSP, if evidence demonstrating its effectiveness were available. Potential barriers to neurocognitive training program adoption included fatigue, cognitive overload, lack of familiarity with the technology used for delivering the intervention, and immediate postoperative pain and stress. Implementation facilitators would include patient education about the intervention, incentives for its use, and daily reminders. The study identified several guiding principles for addressing patients' and clinicians' barriers to effectively implementing a neurocognitive training intervention to mitigate PPSP after surgery. To ensure the sustainability of neurocognitive interventions for preventing PPSP, such interventions would need to be adapted to meet patients' and clinicians' needs within the perioperative context.


[Application of direct electric current and intravenous ozone therapy in the complex treatment of destructive forms of acute pancreatitis in experiment].
The results of experimental study which have carried out on 40 outbread dogs were analyzed in this thesis. Modeling of destructive pancreatitis in animals has been achieved via canalicular-hypertensive model by S.A. Shalimov. 4 series of experimental study were made to achieve the targeted goal. The first series 10 dogs without treatment, the second series 10 dogs in which conventional conservative therapy was used for the treatment of acute experimental destructive pancreatitis in animals, the third series 10 dogs that underwent intravenous ozone therapy in the complex together with medication therapy, the forth series the effectiveness of combined administration of intravenous ozone therapy and small doses of direct current in 10 dogs was evaluated. Combined administration of small doses of DC and intravenous ozone therapy in the complex treatment of destructive pancreatitis shows antiphlogistic action, favors accelerated rejection of necrotic tissue, remits inflammatory process as well as encourages regeneration process in pancreas whereby allows to decrease the mortality in experimental animals from 60% to 20%.


ASB2 targets filamins A and B to proteasomal degradation.
The ordered series of proliferation and differentiation from hematopoietic progenitor cells is disrupted in leukemia, resulting in arrest of differentiation at immature proliferative stages. Characterizing the molecular basis of hematopoietic differentiation is therefore important for understanding and treating disease. Retinoic acid induces expression of ankyrin repeat-containing protein with a suppressor of cytokine signaling box 2 (ASB2) in acute promyelocytic leukemia cells, and ASB2 expression inhibits growth and promotes commitment, recapitulating an early step critical for differentiation. ASB2 is the specificity subunit of an E3 ubiquitin ligase complex and is proposed to exert its effects by regulating the turnover of specific proteins; however, no ASB2 substrates had been identified. Here, we report that ASB2 targets the actin-binding proteins filamin A and B for proteasomal degradation. Knockdown of endogenous ASB2 in leukemia cells delays retinoic acid-induced differentiation and filamin degradation; conversely, ASB2 expression in leukemia cells induces filamin degradation. ASB2 expression inhibits cell spreading, and this effect is recapitulated by knocking down both filamin A and filamin B. Thus, we suggest that ASB2 may regulate hematopoietic cell differentiation by modulating cell spreading and actin remodeling through targeting of filamins for degradation.


Psychometric evaluation of the OM8-30 questionnaire in Dutch children with otitis media.
The Dutch translation of the OM8-30 questionnaire, originally developed in the UK on a large clinical sample, has been applied for validation in an ENT sample, with the aim of assessing otitis media impact and identifying treatment needs in children suffering from chronic otitis media (OM) and/or upper respiratory tract infections (URTI). Caregivers of 246 children completed the OM8-30 and also the generic Strengths and Difficulties Questionnaire (SDQ), prior to otolaryngologist consultation. Factor analysis confirmed the hypothesized six-factor structure, accounting for 55.5% of the variance. The internal consistency was satisfactory to good for all of the physical and developmental facets (alpha-values > or = 0.68). The correlation matrix with the SDQ scales and total difficulties score showed significant relationships for almost all of the OM8-30 developmental facets and sub-aggregate (Ps < 0.01), supporting the concurrent validity of the OM8-30 as a measure of impact in otitis media. This first examination of the Dutch OM8-30 shows that the psychometric characteristics are sufficiently good for the assessment of disease impact, and that this can be subdivided into impact on physical health and on developmental aspects. Recommendations for further research include the study of confounders such as hearing, age and previous operations so that these can be adjusted out, and the determination of which subgroup of children may benefit from tympanostomy tubes.


[Effects of a few nutritional factors on content of coenzyme Q10 by tobacco plant cells in suspension culture].
With suspension cultured cells of tobacco (Nicoliana Tobacum L.), effects of inorganic phosphate, nitrogen sources and carbon source on cell growth and CoQ10 content were investigated. It showed that, When treated with 30 g/L of sucrose, the total amount of CoQ10 was highest (8212 g/L); and the cell biomass and CoQ10 content were 19.8 micrograms/L, 414.7 micrograms/g(dwt) respectively. When treated 340 mg/L of KH2PO4, the cell biomass, the content and total amount of CoQ10 were 21.04 g/L, 514.5 micrograms/g(dwt) and 10824 micrograms/L respectively. When treated with the ratio of NH4+/NO3- was 1:2, the cell biomass, the content and total amount of CoQ10 were 21.04 g/L, 514.3 micrograms/g(dwt) and 10,820 micrograms/L respectively. The high ration of NH4+/NO3- was suitable for the formation of CoQ10, but not for the cell growth.


Morphology, Loadability, and Releasing Profiles of CalliSpheres Microspheres in Delivering Oxaliplatin: An In Vitro Study.
This study aimed to explore the morphology, loadability, and releasing profiles of CalliSpheres microspheres in delivering oxaliplatin. Varied amount (20, 40, 60, and 80 mg oxaliplatin) and concentration (1.25, 2.5, 5.0 mg/mL oxaliplatin) of oxaliplatin were mixed with CalliSpheres microspheres with 3 sizes (50-150 μm, 100-300 μm, and 300-500 μm) to measure the loadability. Of all, 20 mg oxaliplatin-loaded CalliSpheres microspheres with 3 sizes was prepared to measure the releasing profiles, meanwhile, fetal bovine serum was added to determine the effect of serum on oxaliplatin releasing. The morphology and size distribution of CalliSpheres microspheres with 3 sizes before and after 20 mg oxaliplatin loading were detected. Oxaliplatin amount was negatively correlated with loading efficiency with highest loadability in 20 mg oxaliplatin group (maximum 40% in 50-100 µm CalliSpheres microspheres, 52% in 100-300 µm CalliSpheres microspheres, and 52% in 300-500 µm CalliSpheres microspheres), while oxaliplatin concentration was positively associated with loading efficiency. Similar drug-releasing profiles were observed among oxaliplatin-loaded CalliSpheres microspheres with 3 sizes, and a rapid drug release was discovered in CalliSpheres microspheres with 3 sizes as well. We also found that fetal bovine serum did not affect the drug-releasing profiles of oxaliplatin-loaded CalliSpheres microspheres. In addition, CalliSpheres microspheres was modified a little to ellipse shape and less smooth after oxaliplatin loading, and it was enlarged to some extent. This study discloses drug loadability, releasing profiles, and morphology change of CalliSpheres microspheres for delivering oxaliplatin, which provides potential evidences for application of oxaliplatin-loaded drug-eluting beads in clinical practice.


[A Case Report of an Undifferentiated Pancreatic Carcinoma Diagnosed as a Solid Pseudopapillary Neoplasm before Surgery].
A 37-year-old man visited a previous hospital because of left abdominal pain. A contrast-enhanced CT scan revealed a 7 cm solid tumor in the pancreas body, and the patient was referred to our hospital. EUS-FNA showed that the tumor cells were positive for b-catenin in the nuclei, as well as for CD10 and CD56. On the other hand, the cells were negative for chromogranin A and synaptophysin. This is the typical immunohistochemical pattern of a solid pseudopapillary neoplasm(SPN). Therefore, we diagnosed this case as SPN before surgery. As the tumor progressed rapidly in 2 months, we performed distal pancreatectomy, total gastrectomy, and partial liver resection of the left lateral segment because of suspicious invasion of the pancreatic tumor to the stomach and the liver. On histological examination of the resected specimen, tumor invasion to the stomach was apparent, but the tumor did not invade the liver. Immunohistochemical staining showed the same SPN pattern as the EUS-FNA results. We identified small and uniform tumor cells, although no pseudopapillary pattern was observed with HE staining. Finally, we diagnosed this case as an undifferentiated carcinoma. We need to consider the possibility of malignant transformation or undifferentiated carcinoma even when a tumor is diagnosed as SPN on EUS-FNA.


Single nucleotide polymorphisms (SNPs) of pro-inflammatory/anti-inflammatory and thrombotic/fibrinolytic genes in patients with acute ischemic stroke in relation to TOAST subtype.
The genetic basis of complex diseases like ischemic stroke probably consists of several predisposing risk factors, such as genes involved in inflammation and thrombotic pathways. On this basis the aim of our study was to evaluate the role of SNPs (single nucleotide polymorphisms) of some pro-inflammatory/anti-inflammatory and coagulation/fibrinolytic genes in patients with acute ischemic stroke. The study population consisted of 144 consecutive Caucasian adult patients who were hospitalized in the Internal Medicine Department at the University of Palermo between November 2006 and January 2008, and who met inclusion criteria. The cases were patients admitted with a diagnosis of acute ischemic stroke, and age-matched (± 3 years) control subjects: patients admitted to our Internal Medicine Department for any cause other than acute cardiovascular and cerebrovascular events and for routine checkup examinations. Molecular analysis of alleles at the -308 nucleotide (-308G/A) of TNF-α gene, -1082/-819 haplotypes of IL-10 gene, IL-1RN exon 2 VNR polymorphism, alleles at the -174 nucleotide (-174G/C) of IL-6 gene, PAI-1675 5G/4G polymorphism, alleles at the -7351 nucleotide (-7351C/T) of tPA gene was undertaken in both patient groups. We analyzed 96 subjects with acute ischemic stroke and 48 control subjects. We observed a significantly higher frequency of IL-10 1082 AA genotype in stroke patients with a significant risk trend. We also reported a higher frequency in stroke subjects with a significant risk trend of the TPA 7351-CT genotype and of IL-1RN-VNTR 86 bp 2/2 genotype. Moreover, we observed a significant relationship with TOAST subtype only with regard to CC TPA genotype and 1/1 IL-1 VNTR 86 bp and lacunar strokes. Ischemic stroke is a common multifactor disease, which is affected by a number of genetic mutations and environmental factors. Our findings showing a relationship between pro-inflammatory/anti-inflammatory and thrombotic/fibrinolytic genes SNPs and ischemic stroke may contribute to delineate a possible stroke risk profile in subjects with cerebrovascular risk factors.


Geographic information systems (GIS) in assessing dental health.
The present study investigated the distribution profile of dental caries and its association with areas of social deprivation at the individual and contextual level. The cluster sample consisted of 1,002 12-year-old schoolchildren from Piracicaba, SP, Brazil. The DMFT Index was used for dental caries and the Care Index was used to determine access to dental services. On the individual level, variables were associated with a better oral status. On the contextual level, areas were not associated with oral status. However, maps enabled determining that the central districts have better social and oral conditions than the deprived outlying districts.


Brains, innovations and evolution in birds and primates.
Several comparative research programs have focused on the cognitive, life history and ecological traits that account for variation in brain size. We review one of these programs, a program that uses the reported frequency of behavioral innovation as an operational measure of cognition. In both birds and primates, innovation rate is positively correlated with the relative size of association areas in the brain, the hyperstriatum ventrale and neostriatum in birds and the isocortex and striatum in primates. Innovation rate is also positively correlated with the taxonomic distribution of tool use, as well as interspecific differences in learning. Some features of cognition have thus evolved in a remarkably similar way in primates and at least six phyletically-independent avian lineages. In birds, innovation rate is associated with the ability of species to deal with seasonal changes in the environment and to establish themselves in new regions, and it also appears to be related to the rate at which lineages diversify. Innovation rate provides a useful tool to quantify inter-taxon differences in cognition and to test classic hypotheses regarding the evolution of the brain.


Negative photoconductivity induced by surface plasmon polaritons in Ag nanowire macrobundles.
We study experimentally and theoretically the transport properties of Ag nanowire macrobundles in the presence of light irradiation. We have observed significant negative photoconductivity induced by the interaction between electrons and the excited surface plasmon polaritons (SPPs). As temperature T increases from 77 K to 304 K, the dark resistivity rhod without light irradiation increases linearly with T, and the resistivity change Deltarho due to light irradiation decreases nonlinearly with increasing T. The current change |DeltaI| due to light irradiation, which is proportional to the laser intensity, also decreases nonlinearly with increasing T. We explain well the experimental results using our proposed model with a new scattering channel due to the interaction between electrons and SPPs. Both our experimental and theoretical results reveal the novel phenomena due to the combination of photonics and electronics properties of Ag nanowires and they will be useful for scientific research, and technical applications.


Colored filter glasses: an intercomparison of glasses made by different manufacturers.
Specifications of about eight-hundred colored glasses made by thirteen manufacturers are examined and intercompared. The internal spectral transmittances of typical glasses are plotted in a series of forty-four diagrams. A log (internal density) vs wavelength representation is used. Curves with similar characteristics are grouped together in the same diagram. The internal spectral transmittances for a number of different thicknesses of each glass type can be read directly from the diagram. The curves are identified in a table, which lists the equivalent thicknesses of glasses yielding approximately the same transmittance. Such information facilitates the choice of filter components of reasonable thickness.


Palliative Excellence in Alzheimer Care Efforts (PEACE): a program description.
Hospice is the standard method for providing quality end-of-life care in the United States. However, studies reveal that persons with dementia are infrequently referred to hospice, that barriers exist to increasing hospice utilization in this population, and that patients with dementia would benefit from hospice or hospice-like services earlier in the disease course. The Palliative Excellence in Alzheimer Care Efforts (PEACE) program responds to these deficiencies, striving to improve end-of-life care of persons with dementia and to integrate palliative care into the primary care of patients with dementia throughout the course of the illness. The PEACE program is a disease management model for dementia that incorporates advance planning, patient-centered care, family support, and a palliative care focus from the diagnosis of dementia through its terminal stages. PEACE is coordinated through the primary care geriatrics practice of the University of Chicago. Patients and caregivers are interviewed every 6 months for 2 years, and a postdeath interview is conducted with caregivers. These interviews assess care domains important for the optimal care of persons with dementia and their caregivers. A nurse coordinator reviews interviews and provides feedback to physicians, facilitating enhanced individual care and continuous quality improvement for the practice. Initial feedback suggests patients have adequate pain control, satisfaction with quality of care, appropriate attention to prior stated wishes, and death occurring in the patient's location of choice. Families voiced similar high marks regarding quality of care. This program demonstrates an innovative model of providing quality palliative care for dementia patients and their caregivers.


Quantitation of branched-chain alpha-keto acids as their N-methylquinoxalone derivatives: comparison of O- and N-alkylation versus -silylation.
Quantitative estimation of isotopic enrichment and concentrations of keto analogs of branched-chain amino acids in biological fluid has been used for the study of protein metabolism in animal and human studies. At present, O-trimethylsilyl-quinoxalinol derivative is used widely in the quantification of branched-chain alpha-keto acids. In the present study, N-methyl-quinoxalone derivative was developed and its use in quantification in human studies verified. O-phenylenediamine and alpha-keto acid react in acidic media to yield phenolic and amide tautomers. O-trimethylsilyl-quinoxalinol derivative of the phenolic tautomer is used at present for quantification by chemical ionization/selected ion monitoring. We have prepared N-methyl-quinoxalone derivative using N,N-dimethyl formamide dimethyl acetal. This derivative is characterized by a major amide form and a minor phenolic form. The mass spectrum has a characteristic fragment, which facilitates easy identification and quantitation by electron impact/selected ion monitoring. Because m/z 174 was observed as the base peak for alpha-ketoisocaproate, alpha-keto-beta-methylvalerate and alpha-ketoisovalerate, "single ion monitoring' could be performed for the quantification of isotopic enrichment as well as plasma concentration of these three branched-chain alpha-keto acids. Isotopic enrichment from 0.25 to 7.5 at% excess could be measured easily, with an average coefficient of variation of less than 8%. Plasma concentrations as low as 10 microM l-1 in a 200-microliters aliquot could be measured. Methyl migration was an interesting feature of the mass spectrometric fragmentation pattern of the alpha-keto acids. The mechanism of methyl migration is proposed and discussed. This paper also describes some of the studies involved in the formation of isomeric O- and N-alkyl, -quinoxaline and -quinoxalone using a number of N,N-dimethyl formamide dialkyl acetals.


The Verapamil in Hypertension and Atherosclerosis Study (VHAS): results of long-term randomized treatment with either verapamil or chlorthalidone on carotid intima-media thickness.
It is unclear whether the carotid intima-media thickness can be influenced by antihypertensive treatment and whether some antihypertensive agents, such as calcium antagonists, may have a greater effect on this parameter than others, such as diuretics. The present paper reports the principal results of the ultrasound substudy of the randomized, prospective, controlled, Verapamil in Hypertension and Atherosclerosis Study (VHAS). In 498 hypertensive patients in eight Italian centres, randomized to either verapamil (240 mg once a day) or chlorthalidone (25 mg once a day), a B-mode ultrasound scan was performed according to a standardized procedure at baseline and after 3, 12, 24, 36 and 48 months of treatment. The maximum intima-media thicknesses of the far walls of common, bifurcation and internal carotid arteries were measured bilaterally, and the following indices calculated: the mean thickness at the six measured sites, the mean thickness at the common and bifurcation sites and the single maximum thickness. The primary endpoint for treatment efficacy was the slope of the change over 4 years (rate of change, mm/year), corrected by using the initial mean over the six sites (baseline + 3 months) as a covariate (mm/year per mm). The patients were also classified into three strata according to their baseline single maximum thickness: those with normal carotid arteries (single maximum ( 1 mm), those with thickened carotid arteries (single maximum > 1 and < or = 1.5 mm and those with carotid plaques (single maximum > 1.5 mm). Among the 456 patients with satisfactory baseline ultrasound readings, 33% were classified with normal carotid arteries, 27% with thickened carotid arteries and 40% with plaques. In the intention-to-treat population (377 patients with ultrasound measurements taken on at least three different occasions over a period of at least 2 years), the rate of change in the mean thickness at the six sites measured was rather small (0.015 mm/year), but significantly (P < 0.05) smaller in patients with plaques (0.003 mm/year) than in patients with thickened or with normal carotids (0.023 and 0.025 mm/year, respectively). When related to initial values, the rate of change in the mean thickness at the six sites had a negative slope (-0.059 mm/year per mm, P < 0.01). Although rates of change in the carotid intima-media thickness in unstratified patients were not different in those treated with verapamil or with chlorthalidone, when changes in the mean thickness of six sites were related to the initial value, the slope of this relationship was significantly different in the two treatment groups (verapamil -0.082 versus chlorthalidone -0.037 mm/year per mm, P < 0.02). The blood pressure-lowering effect of the two randomized treatments was similar. Taking fatal and nonfatal, major and minor cardiovascular events together, there were 19 events in the verapamil group and 35 in the chlorthalidone group, with a significantly (P < 0.01) greater incidence in patients with plaques, and among patients with plaques in those who were randomized to chlorthalidone (P < 0.05). In accord with evidence from animal models of atherosclerosis, the calcium antagonist verapamil was more effective than the diuretic chlorthalidone in promoting regression of thicker carotid lesions. Changes in the carotid intima-media thickness were small in both groups, and the differences between the changes under the two treatments were consequently small, but the observation that these small differences in carotid wall changes were paralleled by differences in the incidence of cardiovascular events (better intima-media thickness regression with verapamil paralleled by a lower cardiovascular event rate) suggests that even small effects on carotid plaques may have clinical and prognostic relevance.


Exploration of the Conformational Scenario for α-, β-, and γ-Cyclodextrins in Dry and Wet Conditions, from Monomers to Crystal Structures: A Quantum-Mechanical Study.
Cyclodextrins (CDs) constitute a class of cyclic oligosaccharides that are well recognized and largely applied in the drug delivery field, thanks to their biocompatibility, low cost, and the possibility to be derivatized in order to tune and optimize the complexation/release of the specific drug. The conformational flexibility of these systems is one of their key properties and requires a cost-effective methodology to be studied by combining the accuracy of results with the possibility of exploring a large set of conformations. In the present paper, we have explored the conformational potential energy surface of the monomers and dimers of α-, β-, and γ-cyclodextrins (i.e., 6, 7, and 8 monomeric units, respectively) by means of fast but accurate semiempirical methods, which are then refined by state-of-the-art DFT functionals. Moreover, the crystal structure is considered for a more suitable comparison with the IR spectrum experimentally recorded. Calculations are carried out in the gas phase and in water environments, applying both implicit and explicit treatments. We show that the conformation of the studied molecules changes from the gas phase to the water, even if treated implicitly, thus modifying their complexation capability.


DNA fragments in the blood plasma of cancer patients: quantitations and evidence for their origin from apoptotic and necrotic cells.
Increased levels of DNA fragments have frequently been found in the blood plasma of cancer patients. Published data suggest that only a fraction of the DNA in blood plasma is derived from cancer cells. However, it is not known how much of the circulating DNA is from cancer or from noncancer cells. By quantitative methylation-specific PCR of the promoter region of the CDKN2A tumor suppressor gene, we were able to quantify the fraction of plasma DNA derived from tumor cells. In the plasma samples of 30 unselected cancer patients, we detected quantities of tumor DNA from only 3% to as much as 93% of total circulating DNA. We investigated possible origins of nontumor DNA in the plasma and demonstrate here a contribution of T-cell DNA in a few cases only. To investigate the possibility that plasma DNA originates from apoptotic or necrotic cells, we performed studies with apoptotic (staurosporine) and necrotic (staurosporine plus oligomycin) cells in vitro and with mice after induction of apoptotic (anti-CD95) or necrotic (acetaminophen) liver injury. Increasing amounts of DNA were found to be released in the supernatants of cells and in the blood plasma samples of treated animals. A clear discrimination of apoptotic and necrotic plasma DNA was possible by gel electrophoresis. The same characteristic patterns of DNA fragments could be identified in plasma derived from different cancer patients. The data are consistent with the possibility that apoptotic and necrotic cells are a major source for plasma DNA in cancer patients.


The discrimination of self from other as a component of empathy.
Despite the centrality of empathy in human social life, there is no widely agreed definition or characterization of the concept of empathy. A common thread in many of the proposed definitions, however, is that empathy presupposes the discrimination of self and other on the grounds that, to empathize with another individual, the mental state of the target individual must first be distinguished from the empathizer's own mental state. The purpose of this study is to investigate this proposal empirically. We employed a paradigm in which participants rated the emotional valence and degree of arousal of 93 facial expressions of mental states. We asked participants to infer the mental state represented by each facial expression (the Other condition) as well as to describe the effect of the expression on their own mental state (the Self condition). An absolute difference score between the Other and the Self conditions was used as an index of a capacity for self-other discrimination. Empathy was measured using the Interpersonal Reactivity Index. Results show that individuals high in trait empathy discriminate between self and other to a significantly greater degree when judging mental states than individuals low in trait empathy. This suggests that the capacity for self-other discrimination may be a component of the capacity for empathy and that future investigations of the concept of empathy ought to retain it. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


An optimized photon pair source for quantum circuits.
We implement an ultrafast pulsed type-II parametric down conversion source in a periodically poled KTP waveguide at telecommunication wavelengths with almost identical properties between signal and idler. As such, our source resembles closely a pure, genuine single mode photon pair source with indistinguishable modes. We measure the joint spectral intensity distribution and second order correlation functions of the marginal beams and find with both methods very low effective mode numbers corresponding to a Schmidt number below 1.16. We further demonstrate the indistinguishability as well as the purity of signal and idler photons by Hong-Ou-Mandel interferences between signal and idler and between signal/idler and a coherent field, respectively. Without using narrowband spectral filtering, we achieve a visibility for the interference between signal and idler of 94.8% and determine a purity of more than 80% for the heralded single photon states. Moreover, we measure raw heralding efficiencies of 20.5% and 15.5% for the signal and idler beams corresponding to detector-loss corrected values of 80% and 70%.


Catalytic Conversion of Levulinic Acid to Pyrrolidone under Mild Conditions with Disordered Mesoporous Silica-Supported Pt Catalyst.
Catalytic conversion of biomass-derived levulinic acid (LA) into high-valued 5-methylpyrrolidones has become an attractive case in studies of biomass utilization. Herein, we developed a disordered mesoporous Pt/MNS catalyst for this reductive amination process under room temperature and atmospheric pressure of hydrogen. The disordered mesoporous structures in support of Pt/MNS catalyst led the formation of highly dispersed Pt species via confinement effect, providing high specific area for enhancing the catalytic sites. With the synergistic effect between highly dispersed Pt species and mesoporous structures, 5-methylpyrrolidones were successfully synthesized from biomass-derived LA and primary amines with high selectivity. Mechanism studies indicated that introducing protonic acid would promote the reductive-amination process, and enamine intermediates could be detected during the in-situ DRIFT tests. Density functional theory (DFT) calculation confirmed that the hydrogenation of enamine intermediate was more accessible than that of imide intermediates, leading the excellent performance of the Pt/MNS catalyst. This work provided a green method to produce 5-methylpyrrolidone and revealed the impact of catalyst structural characteristics on the reaction process.


Innovations in the endoscopic management of bladder cancer: is the era of white light cystoscopy over.
Bladder cancer is the most common tumor of the urinary tract, with a worldwide incidence of 8.6 x 100000 in men and 2.6 x 100000 in women (1). The majority of patients (75-85%) present as non-muscle invasive bladder cancer (NMIBC); within this category the most represented stage is Ta (70%), followed by T1 (20%) and, less frequently, carcinoma in situ (CIS) (10%) (2). The diagnosis of NMIBC and, more generally, of bladder cancer, depends on urine cytology and endoscopic examination with histological evaluation of the resected tissue. Clearly, an optimal cystoscopy with accurate transurethral resection (TUR) is of great importance in order to improve the detection rate and to reduce the probability of recurrence and progression. Today the cystoscopy is routinely performed with the white light technique (WLC), the same of about 80 years ago (3). Several studies have demonstrated that an initial TUR with WLC can miss small papillary lesions and, particularly, flat lesions such as CIS. Moreover, recurrence rates of non-muscle invasive bladder cancer (NMIBC) are directly related to the possibility of achieving a complete resection: residual cancer is present in a large percentage of re-TUR, showing a not so good performance of resection with this method. For these reasons new methodologies have been investigated in order to improve the sensitivity and specificity of WLC, such as photodynamic diagnosis (PDD), narrow band imaging (NBI), optical coherence tomography (OCT) and CT virtual cystoscopy. Some of them have been well established and supported by consistent literature while others are still to be viewed as experimental. The purpose of this review is to investigate the state of the art of these new techniques.


Saturation function-based continuous control on fixed-time synchronization of competitive neural networks.
Currently, through proposing discontinuous control strategies with the signum function and discussing separately short-term memory (STM) and long-term memory (LTM) of competitive artificial neural networks (ANNs), the fixed-time (FXT) synchronization of competitive ANNs has been explored. Note that the method of separate analysis usually leads to complicated theoretical derivation and synchronization conditions, and the signum function inevitably causes the chattering to reduce the performance of the control schemes. To try to solve these challenging problems, the FXT synchronization issue is concerned in this paper for competitive ANNs by establishing a theorem of FXT stability with switching type and developing continuous control schemes based on a kind of saturation functions. Firstly, different from the traditional method of studying separately STM and LTM of competitive ANNs, the models of STM and LTM are compressed into a high-dimensional system so as to reduce the complexity of theoretical analysis. Additionally, as an important theoretical preliminary, a FXT stability theorem with switching differential conditions is established and some high-precision estimates for the convergence time are explicitly presented by means of several special functions. To achieve FXT synchronization of the addressed competitive ANNs, a type of continuous pure power-law control scheme is developed via introducing the saturation function instead of the signum function, and some synchronization criteria are further derived by the established FXT stability theorem. These theoretical results are further illustrated lastly via a numerical example and are applied to image encryption.


Adaptively loaded SP-offset-QAM OFDM for IM/DD communication systems.
In this paper, we propose adaptively loaded set-partitioned offset quadrature amplitude modulation (SP-offset-QAM) orthogonal frequency division multiplexing (OFDM) for low-cost intensity-modulation direct-detection (IM/DD) communication systems. We compare this scheme with multi-band carrier-less amplitude phase modulation (CAP) and conventional OFDM, and demonstrate >40 Gbit/s transmission over 50-km single-mode fiber. It is shown that the use of SP-QAM formats, together with the adaptive loading algorithm specifically designed to this group of formats, results in significant performance improvement for all these three schemes. SP-offset-QAM OFDM exhibits greatly reduced complexity compared to SP-QAM based multi-band CAP, via parallelized implementation and minimized memory length for spectral shaping. On the other hand, this scheme shows better performance than SP-QAM based conventional OFDM at both back-to-back and after transmission. We also characterize the proposed scheme in terms of enhanced tolerance to fiber intra-channel nonlinearity and the potential to increase the communication security. The studies show that adaptive SP-offset-QAM OFDM is a promising IM/DD solution for medium- and long-reach optical access networks and data center connections.


New routes to food gels and glasses.
We describe the possibility to create solid-like protein samples whose structural and mechanical properties can be varied and tailored over an extremely large range in a very controlled way through an arrested spinodal decomposition process. We use aqueous lysozyme solutions as a model globular protein system. A combination of video microscopy, small-angle neutron and X-ray scattering and reverse Monte Carlo modeling is used to characterize the structure of the bicontinuous network with two coexisting phases of a dilute protein solution and a glassy or arrested dense protein backbone at all relevant length scales. Rheological measurements are then used to determine the complex mechanical response of these protein gels as a function of protein concentration and quench temperature. While in particular the origin of the dependence of the mechanical properties on quench depth and concentration is not well understood currently, it seems ultimately connected to the particular bicontinuous structure of the arrested spinodal network created by the interplay between the early stage of a spinodal decomposition and the position of the glass line. We then generalize this behavior and discuss how this could open up new routes to prepare gel-like food systems with adjustable structural and mechanical properties. We present results from a first feasibility study where we use a depletion interaction caused by the addition of small non-adsorbing polymers to suspensions of casein micelles in order to create food gels with tunable structural and mechanical properties through an arrested spinodal decomposition process.


[Appearance of parakeratosis cells in cervical smears following hormonal therapy and its significance].
Between 1971 and 1973 19 (3,97%) of 492 senile women with atrophic and inflammatory degenerative vaginal epithelium developed parakeratosis cells after administration of estrogen. These benign cellular changes seem to originate in reserve cells or immature metaplastic squamous epithelia which could explain why these cells are mistaken for small cell carcinoma in situ or immature carcinoma. The criteria most helpful for correct cytologic diagnostics are a clean slide background and an abundance of immature metaplastic squamous epithelia with excentrically located nuclei. Operative diagnostic measures are advisable only if after renewed administration of estrogen similar cells are to be found in the gynecologic smear.


Isolation of an enzyme complex with carbon monoxide dehydrogenase activity containing corrinoid and nickel from acetate-grown Methanosarcina thermophila.
Fast protein liquid chromatography of cell extract from methanol- or acetate-grown Methanosarcina thermophila resolved two peaks of CO dehydrogenase activity. The activity of one of the CO dehydrogenases was sixfold greater in acetate-grown compared with methanol-grown cells. This CO dehydrogenase was purified to apparent homogeneity (70 mumol of methyl viologen reduced per min per mg of protein) and made up greater than 10% of the cellular protein of acetate-grown cells. The native enzyme (Mr 250,000) formed aggregates with an Mr of approximately 1,000,000. The enzyme contained five subunits (Mrs 89,000, 71,000, 60,000, 58,000, and 19,000), suggesting a multifunctional enzyme complex. Nickel, iron, cobalt, zinc, inorganic sulfide, and a corrinoid were present in the complex. The UV-visible spectrum suggested the presence of iron-sulfur centers. The electron paramagnetic resonance spectrum contained g values of 2.073, 2.049, and 2.028; these features were broadened in enzyme that was purified from cells grown in the presence of medium enriched with 61Ni, indicating the involvement of this metal in the spectrum. The pattern of potassium cyanide inhibition indicated that cyanide binds at or near the CO binding site. The properties of the enzyme imply an involvement in the dissimilation of acetate to methane, possibly by cleavage of acetate or activated acetate.


Complete sequences of organelle genomes from the medicinal plant Rhazya stricta (Apocynaceae) and contrasting patterns of mitochondrial genome evolution across asterids.
Rhazya stricta is native to arid regions in South Asia and the Middle East and is used extensively in folk medicine to treat a wide range of diseases. In addition to generating genomic resources for this medicinally important plant, analyses of the complete plastid and mitochondrial genomes and a nuclear transcriptome from Rhazya provide insights into inter-compartmental transfers between genomes and the patterns of evolution among eight asterid mitochondrial genomes. The 154,841 bp plastid genome is highly conserved with gene content and order identical to the ancestral organization of angiosperms. The 548,608 bp mitochondrial genome exhibits a number of phenomena including the presence of recombinogenic repeats that generate a multipartite organization, transferred DNA from the plastid and nuclear genomes, and bidirectional DNA transfers between the mitochondrion and the nucleus. The mitochondrial genes sdh3 and rps14 have been transferred to the nucleus and have acquired targeting presequences. In the case of rps14, two copies are present in the nucleus; only one has a mitochondrial targeting presequence and may be functional. Phylogenetic analyses of both nuclear and mitochondrial copies of rps14 across angiosperms suggests Rhazya has experienced a single transfer of this gene to the nucleus, followed by a duplication event. Furthermore, the phylogenetic distribution of gene losses and the high level of sequence divergence in targeting presequences suggest multiple, independent transfers of both sdh3 and rps14 across asterids. Comparative analyses of mitochondrial genomes of eight sequenced asterids indicates a complicated evolutionary history in this large angiosperm clade with considerable diversity in genome organization and size, repeat, gene and intron content, and amount of foreign DNA from the plastid and nuclear genomes. Organelle genomes of Rhazya stricta provide valuable information for improving the understanding of mitochondrial genome evolution among angiosperms. The genomic data have enabled a rigorous examination of the gene transfer events. Rhazya is unique among the eight sequenced asterids in the types of events that have shaped the evolution of its mitochondrial genome. Furthermore, the organelle genomes of R. stricta provide valuable genomic resources for utilizing this important medicinal plant in biotechnology applications.


Surface-Dependent Osteoblasts Response to TiO2 Nanotubes of Different Crystallinity.
One of the major challenges of implantology is to design nanoscale modifications of titanium implant surfaces inducing osseointegration. The aim of this study was to investigate the behavior of rat osteoblasts cultured on anodized TiO2 nanotubes of different crystallinity (amorphous and anatase phase) up to 24 days. TiO2 nanotubes were fabricated on VT1-0 titanium foil via a two-step anodization at 20 V using NH4F as an electrolyte. Anatase-phase samples were prepared by heat treatment at 500 °C for 1 h. VT1-0 samples with flat surfaces were used as controls. Primary rat osteoblasts were seeded over experimental surfaces for several incubation times. Scanning electron microscopy (SEM) was used to analyze tested surfaces and cell morphology. Cell adhesion and proliferation were investigated by cell counting. Osteogenic differentiation of cells was evaluated by qPCR of runt-related transcription factor 2 (RUNX2), osteopontin (OPN), integrin binding sialoprotein (IBSP), alkaline phosphatase (ALP) and osteocalcin (OCN). Cell adhesion and proliferation, cell morphology and the expression of osteogenic markers were affected by TiO2 nanotube layered substrates of amorphous and anatase crystallinity. In comparison with flat titanium, along with increased cell adhesion and cell growth a large portion of osteoblasts grown on the both nanostructured surfaces exhibited an osteocyte-like morphology as early as 48 h of culture. Moreover, the expression of all tested osteogenic markers in cells cultured on amorphous and anatase TiO2 nanotubes was upregulated at least at one of the analyzed time points. To summarize, we demonstrated that amorphous and anodized TiO2 layered substrates are highly biocompatible with rat osteoblasts and that the surface modification with about 1500 nm length nanotubes of 35 ± 4 (amorphous phase) and 41 ± 8 nm (anatase phase) in diameter is sufficient to induce their osteogenic differentiation. Such results are significant to the engineering of coating strategies for orthopedic implants aimed to establish a more efficient bone to implant contact and enhance bone repair.


Schizophrenia and the mirror system: an essay.
We analyze how data on the mirror system for grasping in macaque and human ground the mirror system hypothesis for the evolution of the language-ready human brain, and then focus on this putative relation between hand movements and speech to contribute to the understanding of how it may be that a schizophrenic patient generates an action (whether manual or verbal) but does not attribute the generation of that action to himself. We make a crucial discussion between self-monitoring and attribution of agency. We suggest that verbal hallucinations occur when an utterance progresses through verbal creation pathways and returns as a vocalization observed, only to be dismissed as external since no record of its being created has been kept. Schizophrenic patients on this theory then confabulate the agent.


Development of Domperidone Solid Lipid Nanoparticles: In Vitro and In Vivo Characterization.
Domperidone (DOP) is extensively applied orally in the management of nausea and vomiting. Upon oral administration, its bioavailability is very poor due to its poor solubility in alkaline media. Therefore, the aim of this work was to investigate DOP-loaded solid lipid nanoparticles (DOP-SLNs) in order to sustain its release pattern and to enhance oral bioavailability. DOP-SLNs were prepared using four different lipids. Prepared DOP-SLNs were characterized for "polydispersity index (PDI), particle size, zeta potential, % entrapment efficiency (% EE), and drug release behavior." Differential scanning calorimetry (DSC) study was carried out to illustrate the physical form of DOP and excipients. The morphology of DOP-SLNs was confirmed by scanning electron microscopy (SEM). Pharmacokinetic study on optimized DOP-SLN in comparison to tablet was performed in rats. The "particle size, PDI, zeta potential, and % EE" of optimized formulation (F5) were recorded as 201.4 nm, 0.071, - 6.2 mV, and 66.3%, respectively. DSC thermograms suggested amorphous state of DOP in various SLNs. Surface morphology of SLNs using SEM suggested spherical shape of the nanoparticles within nanometer size range. In vitro release studies confirmed that all SLN formulations possessed a sustained release over a period of 12 h (51.3% from optimized formulation) in comparison with immediate release from conventional tablets (100% after 90 min). Pharmacokinetic study showed significant enhancement in oral absorption of DOP from optimized SLN in comparison with DOP tablet. The enhancement in relative bioavailability of DOP from optimized SLN was 2.62-fold in comparison with DOP tablet.


Changes in insulin-like growth factor-I and -II associated with fat but not lean mass in early old age.
To test the hypothesis that insulin-like growth factors-I and II (IGF-I and II) decline during late midlife and that greater declines are related to higher fat mass and lower lean mass. A total of 1,542 men and women in a British birth cohort study had IGF-I and II measured by immunoassay of blood samples at age 53 and/or 60-64 years. Fat mass, android:gynoid fat ratio, and appendicular lean mass were measured at 60-64 years using dual-energy X-ray absorptiometry (DXA). Associations between changes in IGF-I or II and body composition outcomes were examined using conditional change linear regression models. Mean IGF-I and IGF-II concentrations were lower at 60-64 than at 53 years, by 12.8% for IGF-I and by 12.5% for IGF-II. Larger declines in either IGF-I or II were associated with higher fat mass at 60-64 years. Although higher IGF-I at 53 years was associated with higher lean mass, there was little evidence linking changes in IGF-I or II to lean mass. The findings suggest that IGF-I and II concentrations decline with age, and greater declines are associated with higher fat mass levels. These results provide some evidence for the suggested roles of IGF-I and II in regulating fat mass but not lean mass in older age.


Combining bio- and organocatalysis for the synthesis of piperidine alkaloids.
There is continued interest in developing cascade processes for the synthesis of key chiral building blocks and bioactive natural products (or analogues). Here, we report a hybrid bio-organocatalytic cascade for the synthesis of a small panel of 2-substituted piperidines, relying on a transaminase to generate a key reactive intermediate for the complexity building Mannich reaction.


Unravelling the mechanism of neurotensin recognition by neurotensin receptor 1.
The conformational ensembles of G protein-coupled receptors (GPCRs) include inactive and active states. Spectroscopy techniques, including NMR, show that agonists, antagonists and other ligands shift the ensemble toward specific states depending on the pharmacological efficacy of the ligand. How receptors recognize ligands and the kinetic mechanism underlying this population shift is poorly understood. Here, we investigate the kinetic mechanism of neurotensin recognition by neurotensin receptor 1 (NTS1) using 19F-NMR, hydrogen-deuterium exchange mass spectrometry and stopped-flow fluorescence spectroscopy. Our results indicate slow-exchanging conformational heterogeneity on the extracellular surface of ligand-bound NTS1. Numerical analysis of the kinetic data of neurotensin binding to NTS1 shows that ligand recognition follows an induced-fit mechanism, in which conformational changes occur after neurotensin binding. This approach is applicable to other GPCRs to provide insight into the kinetic regulation of ligand recognition by GPCRs.


Evaluating the Properties of Ginger Protease-Degraded Collagen Hydrolysate and Identifying the Cleavage Site of Ginger Protease by Using an Integrated Strategy and LC-MS Technology.
(1) Methods: An integrated strategy, including in vitro study (degree of hydrolysis (DH) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity) and in vivo study (absorption after oral administration in rats), was developed to evaluate the properties of the fish skin gelatin hydrolysates prepared using different proteases (pepsin, alkaline protease, bromelain, and ginger protease). Meanwhile, in order to identify the hydrolysis site of ginger protease, the peptides in the ginger protease-degraded collagen hydrolysate (GDCH) were comprehensively characterized by liquid chromatography/tandem mass spectrometry (LC-MS) method. (2) Results: The GDCH exhibited the highest DH (20.37%) and DPPH radical scavenging activity (77.73%), and in vivo experiments showed that the GDCH was more efficiently absorbed by the gastrointestinal tract. Further oral administration experiments revealed that GDCH was not entirely degraded to free amino acids and can be partially absorbed as dipeptides and tripeptides in intact forms, including Pro-Hyp, Gly-Pro-Hyp, and X-Hyp-Gly tripeptides. LC-MS results determined the unique substrate specificity of ginger protease recognizing Pro and Hyp at the P2 position based on the amino acids at the P2 position from the three types of tripeptides (Gly-Pro-Y, X-Hyp-Gly, and Z-Pro-Gly) and 136 identified peptides (>4 amino acids). Interestingly, it suggested that ginger protease can also recognize Ala in the P2 position. (3) Conclusions: This study comprehensively evaluated the properties of GDCH by combining in vitro and in vivo strategies, and is the first to identify the cleavage site of ginger protease by LC-MS technique. It provides support for the follow-up study on the commercial applications of ginger protease and bioactivities of the hydrolysate produced by ginger protease.


The Impact of Priming on Speed Reduction on a Ski Slope.
We tested a field-adapted priming procedure (a technique used to subtly activate mental representations and guide behavior) on a ski slope, with the goal of reducing risk behavior in winter sports. At cableway stations, skiers were initially exposed eight times to a prevention poster displaying a logo and a "slow down" message. The "slow down" concept was activated on the ski slope by exposing skiers (or not) 10 times to the logo featured on the poster. We used a radar device to measure the skiers' speed data just before a slope intersection. We hypothesized that the mean speed would be lower in the presence of the logo than in its absence. As predicted, the speed was lower (by 0.9 km/h) when the skiers had been primed (i.e., exposed to the logo). This decrease was relevant, since any reduction in speed downhill will reduce kinetic (impact) energy and thus the risk of injury in a collision. The effect of priming was statistically significant at noon and in the afternoon but not in the morning. Our pilot study is the first to show that a priming procedure can influence the speed of skiers at a dangerous location. Our findings open up new perspectives for the prevention of risk behavior in winter sports.


Fas ligand expression and function in systemic lupus erythematosus.
Mutations in the Fas receptor or its ligand (FasL) lead to lupus-like systemic autoimmune diseases in mice and in some humans. To determine whether a significant number of patients with systemic lupus erythematosus (SLE) have impaired FasL function, we compared T cell effector function by superantigen-activated CD4+ T cell lines or by anti-CD3- and IL-2-generated cytotoxic T cells. No differences were observed between SLE and normal control superantigen-derived CD4+ T cells in either the ability of these cells to up-regulate Fas expression or to induce apoptosis of the Fas-sensitive target B cells. When anti-CD3/IL-2-activated T cells were examined, SLE T cells had a modest reduction (-8%) in T cell cytotoxicity compared with normal controls, but the reduction was similar to the rheumatoid arthritis disease controls. A modest reduction in cytotoxicity was evident in both the Fas and perforin/granzyme pathways as determined by testing Fas-positive and -negative targets as well as by selective blockade of the perforin/granzyme pathway with concanamycin. These results indicate that no specific defects in FasL function are evident in the majority of SLE patients under the in vitro conditions tested. The proportional reduction in FasL and perforin/granzyme function in SLE and rheumatoid arthritis patients following anti-CD3/IL-2 stimulation most likely reflects subtle differences in activation in patient-derived vs normal control T cells.


Electrical conductivity during incipient melting in the oceanic low-velocity zone.
The low-viscosity layer in the upper mantle, the asthenosphere, is a requirement for plate tectonics. The seismic low velocities and the high electrical conductivities of the asthenosphere are attributed either to subsolidus, water-related defects in olivine minerals or to a few volume per cent of partial melt, but these two interpretations have two shortcomings. First, the amount of water stored in olivine is not expected to be higher than 50 parts per million owing to partitioning with other mantle phases (including pargasite amphibole at moderate temperatures) and partial melting at high temperatures. Second, elevated melt volume fractions are impeded by the temperatures prevailing in the asthenosphere, which are too low, and by the melt mobility, which is high and can lead to gravitational segregation. Here we determine the electrical conductivity of carbon-dioxide-rich and water-rich melts, typically produced at the onset of mantle melting. Electrical conductivity increases modestly with moderate amounts of water and carbon dioxide, but it increases drastically once the carbon dioxide content exceeds six weight per cent in the melt. Incipient melts, long-expected to prevail in the asthenosphere, can therefore produce high electrical conductivities there. Taking into account variable degrees of depletion of the mantle in water and carbon dioxide, and their effect on the petrology of incipient melting, we calculated conductivity profiles across the asthenosphere for various tectonic plate ages. Several electrical discontinuities are predicted and match geophysical observations in a consistent petrological and geochemical framework. In moderately aged plates (more than five million years old), incipient melts probably trigger both the seismic low velocities and the high electrical conductivities in the upper part of the asthenosphere, whereas in young plates, where seamount volcanism occurs, a higher degree of melting is expected.


A Novel Microbial Culture Chamber Co-cultivation System to Study Algal-Bacteria Interactions Using Emiliania huxleyi and Phaeobacter inhibens as Model Organisms.
Our understanding of microbial natural environments combines in situ experimentation with studies of specific interactions in laboratory-based setups. The purpose of this work was to develop, build and demonstrate the use of a microbial culture chamber enabling both in situ and laboratory-based studies. The design uses an enclosed chamber surrounded by two porous membranes that enables the comparison of growth of two separate microbial populations but allowing free exchange of small molecules. Initially, we tested if the presence of the macroalga Fucus vesiculosus inside the chamber affected colonization of the outer membranes by marine bacteria. The alga did indeed enrich the total population of colonizing bacteria by more than a factor of four. These findings lead us to investigate the effect of the presence of the coccolithophoric alga Emiliania huxleyi on attachment and biofilm formation of the marine bacterium Phaeobacter inhibens DSM17395. These organisms co-exist in the marine environment and have a well-characterized interdependence on secondary metabolites. P. inhibens attached in significantly higher numbers when having access to E. huxleyi as compared to when exposed to sterile media. The experiment was carried out using a wild type (wt) strain as well as a TDA-deficient strain of P. inhibens. The ability of the bacterium to produce the antibacterial compound, tropodithietic acid (TDA) influenced its attachment since the P. inhibens DSM17395 wt strain attached in higher numbers to a surface within the first 48 h of incubation with E. huxleyi as compared to a TDA-negative mutant. Whilst the attachment of the bacterium to a surface was facilitated by presence of the alga, however, we cannot conclude if this was directly affected by the algae or whether biofilm formation was dependent on the production of TDA by P. inhibens, which has been implied by previous studies. In the light of these results, other applications of immersed culture chambers are suggested.


Prevalence and genetic diversity of rotavirus in Bangladesh during pre-vaccination period, 1973-2023: a meta-analysis.
Rotavirus infection is a major cause of mortality among children under 5 years in Bangladesh. There is lack of integrated studies on rotavirus prevalence and genetic diversity during 1973 to 2023 in Bangladesh. This meta-analysis was conducted to determine the prevalence, genotypic diversity and seasonal distribution of rotavirus during pre-vaccination period in Bangladesh. This study included published articles on rotavirus A, rotavirus B and rotavirus C. We used Medline, Scopus and Google Scholar for published articles. Selected literatures were published between 1973 to 2023. This study detected 12431 research articles published on rotavirus. Based on the inclusion criteria, 29 of 75 (30.2%) studies were selected. Molecular epidemiological data was taken from 29 articles, prevalence data from 29 articles, and clinical symptoms from 19 articles. The pooled prevalence of rotavirus was 30.1% (95% CI: 22%-45%, p = 0.005). Rotavirus G1 (27.1%, 2228 of 8219) was the most prevalent followed by G2 (21.09%, 1733 of 8219), G4 (11.58%, 952 of 8219), G9 (9.37%, 770 of 8219), G12 (8.48%, 697 of 8219), and G3 (2.79%, 229 of 8219), respectively. Genotype P[8] (40.6%, 2548 of 6274) was the most prevalent followed by P[4] (12.4%, 777 of 6274) and P[6] (6.4%, 400 of 6274), respectively. Rotavirus G1P[8] (19%) was the most frequent followed by G2P [4] (9.4%), G12P[8] (7.2%), and G9P[8], respectively. Rotavirus infection had higher odds of occurrence during December and February (aOR: 2.86, 95% CI: 2.43-3.6, p = 0.001). This is the first meta-analysis including all the studies on prevalence, molecular epidemiology, and genetic diversity of rotavirus from 1973 to 2023, pre-vaccination period in Bangladesh. This study will provide overall scenario of rotavirus genetic diversity and seasonality during pre-vaccination period and aids in policy making for rotavirus vaccination program in Bangladesh. This work will add valuable knowledge for vaccination against rotavirus and compare the data after starting vaccination in Bangladesh.


Evaluation of the protein quality of diets containing medium- and long-chain triglyceride in healthy rats.
In this study, protein efficiency ratio and net protein utilization together with the kinetic estimates of protein turnover were used to compare the effect of different protein and fat sources in healthy rats. Male Sprague-Dawley CD rats were pair-fed different diets for 14 d. All diets were isonitrogenous and isocaloric, containing 10.4% protein, 10.9-11.4% fat, 31.9-32.8% carbohydrate and 43.5-44.5% moisture (wt/wt). After 14 d of feeding, protein efficiency ratio, net protein utilization, weight gain, intake, fat and protein content in the whole-body and fractional synthetic rates in various tissues were determined. Animals given diets containing medium-chain triglycerides (MCT) demonstrated decreased weight gain and fat content compared to the pair-fed controls receiving long-chain triglycerides (LCT). No difference was seen in protein content, net protein utilization and fractional synthetic rates in the liver and whole body of these MCT-fed rats when compared to those given LCT. Protein efficiency ratios in both of the MCT groups fed MCT + casein and MCT + soy protein were lower than those in the groups given LCT + casein. Although this study did not include a group for LCT and soy protein, these results suggest that MCT reduces the fat deposition without affecting the whole-body protein content. This may have implications for the treatment of obesity. Secondly, the protein efficiency ratio may not be a useful indicator of dietary protein quality when the fat source is MCT.


Performance of Markov chain-Monte Carlo approaches for mapping genes in oligogenic models with an unknown number of loci.
Markov chain-Monte Carlo (MCMC) techniques for multipoint mapping of quantitative trait loci have been developed on nuclear-family and extended-pedigree data. These methods are based on repeated sampling-peeling and gene dropping of genotype vectors and random sampling of each of the model parameters from their full conditional distributions, given phenotypes, markers, and other model parameters. We further refine such approaches by improving the efficiency of the marker haplotype-updating algorithm and by adopting a new proposal for adding loci. Incorporating these refinements, we have performed an extensive simulation study on simulated nuclear-family data, varying the number of trait loci, family size, displacement, and other segregation parameters. Our simulation studies show that our MCMC algorithm identifies the locations of the true trait loci and estimates their segregation parameters well-provided that the total number of sibship pairs in the pedigree data is reasonably large, heritability of each individual trait locus is not too low, and the loci are not too close together. Our MCMC algorithm was shown to be significantly more efficient than LOKI (Heath 1997) in our simulation study using nuclear-family data.


Variable Volumes of Resected Bone Resulting From Different Total Ankle Arthroplasty Systems.
The increased popularity and success of total ankle arthroplasty (TAA) has resulted in the development of varying TAA hardware designs, many of which include specific bone-sparing or bone-sacrificing features. The goal of this work was to determine differences in the volume of bone removed for implantation of different total ankle arthroplasty hardware systems. Sixteen cadaveric specimens were computed tomography-scanned preoperatively and after total ankle arthroplasty using either an INBONE II, Salto Talaris, STAR, or Zimmer TMTA implant. Geometries of the talus and the distal tibia were manually segmented and converted to 3D bony surface models. The volume of bone removed for each implant was calculated as the difference in volume between the preoperative and postoperative bone models. To account for differences in specimen size, volume was expressed as a percentage of the intact bone. There was a significant difference (P = .049) in the average percent of talar bone removed, with the STAR and INBONE II systems requiring removal of greater volumes of bone. The INBONE II system required significantly (P < .004) more tibial bone resection than the other 3 implants when evaluating a long span of the distal tibia. However, most of this increased bone resection was medullary bone. Close to the articular surface, bone volumes removed for the various tibial components were not significantly different (P = .056). Volume and location of bone removed for different implant systems varied with implant design. Primary bone resection associated with different implant hardware systems varied more on the talar side of the articulation, and the stemmed prosthesis did not result in dramatic increases in periarticular bone resection. Clinicians should weigh the effects of greater or lesser bone resection associated with various implant designs against other factors used for hardware selection.


Isoprostanes quickly normalize after quitting cigarette smoking in healthy adults.
Isoprostanes and in particular 8-epi-PGF2 alpha have been claimed as a useful measure for invivo oxidation injury. While smokers show elevated 8-epi-PGF2 alpha the behaviour during quitting smoking is unknown. We determined 8-epi-PGF2 alpha in 7 healthy adults ready to quit smoking in plasma, serum and urine by means of an enzyme immunoassay after extraction and purification before quitting smoking and during a follow-up period of 4 weeks. After quitting smoking, 8-epi-PGF2 alpha shows a rapid decline within a few days almost completely normalizing within 4 weeks. The cigarette-smoking associated invivo oxidation injury almost completely disappears within 4 weeks of quitting smoking.


Multi-loci diagnosis of acute lymphoblastic leukaemia with high-throughput sequencing and bioinformatics analysis.
High-throughput sequencing (HTS) is considered a technical revolution that has improved our knowledge of lymphoid and autoimmune diseases, changing our approach to leukaemia both at diagnosis and during follow-up. As part of an immunoglobulin/T cell receptor-based minimal residual disease (MRD) assessment of acute lymphoblastic leukaemia patients, we assessed the performance and feasibility of the replacement of the first steps of the approach based on DNA isolation and Sanger sequencing, using a HTS protocol combined with bioinformatics analysis and visualization using the Vidjil software. We prospectively analysed the diagnostic and relapse samples of 34 paediatric patients, thus identifying 125 leukaemic clones with recombinations on multiple loci (TRG, TRD, IGH and IGK), including Dd2/Dd3 and Intron/KDE rearrangements. Sequencing failures were halved (14% vs. 34%, P = 0.0007), enabling more patients to be monitored. Furthermore, more markers per patient could be monitored, reducing the probability of false negative MRD results. The whole analysis, from sample receipt to clinical validation, was shorter than our current diagnostic protocol, with equal resources. V(D)J recombination was successfully assigned by the software, even for unusual recombinations. This study emphasizes the progress that HTS with adapted bioinformatics tools can bring to the diagnosis of leukaemia patients.


Transparent Electrode and Magnetic Permalloy Made from Novel Nanopaper.
We report a novel partial dissolution strategy to liberate uniform cellulose nanofibers with diameter of 5-10 nm from macroscopic cellulose fibers and promote separation of nanofibers in an aqueous environment by forming water-soluble sodium carboxymethylcellulose (CMC) through heterogeneous sodium acetoxylation of cellulose. With the obtained cellulose nanofibers, we fabricated nanopapers which exhibit high optical transparency of 90.5% (@550 nm) with promising mechanical properties and high thermal stability. By directly depositing Ag nanowires on a wet nanofiber sheet, we fabricated a flexible transparent electrode with 86.5% (@550 nm) transparency and 26.2 Ω/sq sheet resistance (Rs). Meanwhile, we studied the magnetic properties of sputter deposited thin film of permalloy on nanopaper which exhibited a similar magnetic coercivity and a close saturation magnetization to conventional silicon dioxide-based permalloy.


Pin1 Regulates IL-5 Induced Eosinophil Polarization and Migration.
Eosinophils become polarized in response to cytokines such IL-5 or eotaxin prior to directional migration. Polarization is preceded by F-actin assembly, but the mechanisms that regulate these events and how the shape change influences cell migration from the peripheral blood into the lung remain unclear. In this study, we show that the prolyl isomerase, Pin1, is required for IL-5-induced Eos polarization and migration. Co-immunoprecipitation and immunofluorescence analysis revealed that Pin1 directly interacts with members of Rho GTPase family. Mouse eosinophils lacking Pin1 or human cells treated with Pin1 inhibitors showed significantly reduced IL-5-induced GTPase activity and cofilin phosphorylation, resulting in reduced F-actin polymerization, cell polarization, and directional migration to chemokines. Our result suggests that Pin1 regulates cytoskeletal re-organization, eosinophil morphology, and cell migration through the modulation of Rho GTPase activity. Targeting Pin1 along with GTPases could provide a new approach to reduce pulmonary Eos accumulation during asthmatic exacerbations.


[The complex grafting of the internal thoracic artery to the coronary arteries].
Among the 34 complex internal thoracic artery (ITA) to coronary artery grafts, there were bilateral (in 20 patients), bifurcated (in 8), sequential (in 4), "free" (in 1), left ITA and right radial artery (in 1). It was performed with the "no-touch" technique to the ascending and transverse aorta, cardiopulmonary bypass with an arterial inflow cannulation to the left common femoral artery, with a beating, warm, and vented heart and severe bradycardia induced by a short acting beta 1-blocker. Two latter factors were used to decrease myocardial oxygen consumption and facilitate construction of the ITA to coronary artery anastomoses. There were no operative mortality.


The effects of high dietary calcium on salt-induced hypertension in rats.
The effects of dietary salt-loading and concurrent administration of dietary calcium on water and electrolyte excretion in Sprague-Dawley rats have been studied. The total salt consumed by salt-loaded rats was significantly higher than that of control rats (P < 0.05). The total salt consumed by salt-loaded calcium fed rats was also higher (P < 0.05) than that of control rats but it was slightly lower (P < 0.05) than the consumption by the salt-loaded. Rats fed only high calcium diet had the least salt consumption. The total water intake was also highest (P < 0.05) in the salt-loaded rats when compared with either control rats, salt-loaded-calcium-fed rats or calcium-fed rats. Urinary water excretion was highest (P < 0.05) in salt-loaded-calcium-fed rats followed by salt-loaded rats and calcium-fed rats while the control rats had the least. Similarly, the sodium excretion was highest in salt-loaded-calcium-fed rats followed by salt-loaded rats and calcium-fed rats and control rats respectively. Potassium excretion was highest in salt-loaded-calcium-fed rats followed by salt-loaded rats and calcium-fed rats while the control rats had the least excretion of potassium. Serum sodium concentrations were identical in all the groups although in salt-loaded rats and salt-loaded-calcium-fed rats the values were slightly higher than those of controls. However, serum potassium concentration was lowest in salt-loaded rats and calcium-fed rats while the values for salt-loaded-calcium-fed rats was not significantly different from that of control. The results of this study suggest that increase in dietary calcium intake reduces the increase in blood pressure resulting from salt-loading and this is accompanied by an increase in water and sodium excretion.


Trait impulsivity and impaired prefrontal impulse inhibition function in adolescents with internet gaming addiction revealed by a Go/No-Go fMRI study.
Recent studies suggest that Internet gaming addiction (IGA) is an impulse disorder, or is at least related to impulse control disorders. In the present study, we hypothesized that different facets of trait impulsivity may be specifically linked to the brain regions with impaired impulse inhibition function in IGA adolescents. Seventeen adolescents with IGA and seventeen healthy controls were scanned during performance of a response-inhibition Go/No-Go task using a 3.0 T MRI scanner. The Barratt Impulsiveness Scale (BIS)-11 was used to assess impulsivity. There were no differences in the behavioral performance on the Go/No-Go task between the groups. However, the IGA group was significantly hyperactive during No-Go trials in the left superior medial frontal gyrus, right anterior cingulate cortex, right superior/middle frontal gyrus, left inferior parietal lobule, left precentral gyrus, and left precuneus and cuneus. Further, the bilateral middle temporal gyrus, bilateral inferior temporal gyrus, and right superior parietal lobule were significantly hypoactive during No-Go trials. Activation of the left superior medial frontal gyrus was positively associated with BIS-11 and Chen Internet Addiction Scale (CIAS) total score across IGA participants. Our data suggest that the prefrontal cortex may be involved in the circuit modulating impulsivity, while its impaired function may relate to high impulsivity in adolescents with IGA, which may contribute directly to the Internet addiction process.


Atypical secretions of the male cephalic labial glands in bumblebees: the case of Bombus (Rhodobombus) mesomelas Gerstaecker (Hymenoptera, Apidae).
In bumblebees, the male secretion of the cephalic labial gland is species-specific. It is highly involved in the nuptial behavior, acting as a sexual attracting pheromone. Therefore, it is also used to accurately identify the species. In contrast to this common scheme, the secretions of Bombus mesomelas are found to be strongly reduced and do not include the most volatile compounds that are present in the secretions of all the other studied bumblebee species. These secretions correspond to cuticular hydrocarbons that can be found in all bumblebee species. This was also the case for another bumblebee species from the same Rhodobombus subgenus: Bombus pomorum. This atypical composition of the male cephalic labial gland secretions seems to indicate that, at least for these two species of Rhodobombus, these secretions are not used to attract virgin females from a long distance, as it is the case for all the other bumblebee species studied.


Effect of shading and light recovery on the growth, leaf structure, and photosynthetic performance of soybean in a maize-soybean relay-strip intercropping system.
Intercropping is an important agronomic practice adopted to increase crop production and resource efficiency in areas with intensive agricultural production. Two sequential field trials were conducted in 2015-2016 to investigate the effect of shading on the morphological features, leaf structure, and photosynthetic characteristics of soybean in a maize-soybean relay-strip intercropping system. Three treatments were designed on the basis of different row configurations A1 ("50 cm + 50 cm" one row of maize and one row of soybean with a 50 cm spacing between the rows), A2 ("160 cm + 40 cm" two rows of maize by wide-narrow row planting, where two rows of soybean were planted in the wide rows with a width of 40 cm, and with 60 cm row spacing was used between the maize and soybean rows), and CK (sole cropping of soybean, with 70 cm rows spacing). Results showed that the photosynthetically active radiation transmittances of soybean canopy at V5 stage under A2 treatment (31.1%) were considerably higher than those under A1 (8.7%) treatment, and the red-to-far-red ratio was reduced significantly under A1 (0.7) and A2 (1.0) treatments compared with those under CK (1.2). By contrast with CK, stem diameter, total aboveground biomass, chlorophyll content and net photosynthetic rate decreased significantly except plant height under A1 and A2. The thickness of palisade tissue and spongy tissue of soybean leaf under A1 and A2 were significantly reduced at V5 stage compared with CK. The leaf thicknesses under A1 and A2 were lower than those in CK by 39.5% and 18.2%, respectively. At the R1 stage of soybean (after maize harvest), the soybean plant height, stem biomass, leaf biomass and petiole biomass under A1 and A2 treatments were still significantly lower than those under CK, but no significant differences were observed in Chl a/b, Pn, epidermis thickness and spongy tissue thickness of soybean leaves in A2 compared with CK. In addition, the soybean yields (g plant-1) under A1 and A2 were 54.69% and 16.83% lower than those in CK, respectively. These findings suggested that soybean plants can regulate its morphological characteristics and leaf anatomical structures under different light environments.


Histidinemia. A case with resolution of myoclonic seizures after treatment with a low-histidine diet.
An infant with histidinemia had a myoclonic seizure disorder that was unresponsive to therapy with anticonvulsants. The seizures stopped promptly after a histidine-restricted diet was instituted. This case suggests that in some individuals with histidinemia, diet therapy may be effective. It is not known what distinguishes this case from previously reported cases in which diet therapy was not effective.